Utilizing machine learning-based QSAR model to overcome standalone consensus docking limitation in beta-lactamase inhibitors screening: a proof-of-concept study.

In virtual drug screening, consensus docking is a standard in-silico approach consisting of a combined result from optimized docking experiments, a minimum of two results combination. Therefore, consensus docking is subjected to a lower success rate than the best docking method due to its mathematical nature, an unavoidable limitation. This study aims to overcome this drawback via random forest, an ensemble machine learning model.

Addressing the Evolution of Cardenolide Formation in Iridoid-Synthesizing Plants: Site-Directed Mutagenesis of PRISEs (Progesterone-5β-Reductase/Iridoid Synthase-like Enzymes) of Plantago Species.

Enzymes capable of processing a variety of compounds enable plants to adapt to diverse environmental conditions. PRISEs (progesterone-5β-reductase/iridoid synthase-like enzymes), examples of such substrate-promiscuous enzymes, are involved in iridoid and cardenolide pathways and demonstrate notable substrate promiscuity by reducing the activated C=C double bonds of plant-borne and exogenous 1,4-enones. In this study, we identified PRISE genes in () and (), and the corresponding enzymes were determined to share a sequence identity of 95%.

Overexpression and RNAi-mediated Knockdown of Two 3β-hydroxy-Δ5-steroid dehydrogenase Genes in Digitalis lanata Shoot Cultures Reveal Their Role in Cardenolide Biosynthesis.

3β-hydroxy-Δ5-steroid dehydrogenases (3βHSDs) are supposed to be involved in -cardenolide biosynthesis. Here, a novel () was isolated from shoot cultures and expressed in . Recombinant 3βHSD1 and 3βHSD2 shared 70% amino acid identity, reduced various 3-oxopregnanes and oxidised 3-hydroxypregnanes, but only 3βHSD2 converted small ketones and secondary alcohols efficiently.

Effects of Lipophilicity and Structural Features on the Antiherpes Activity of Digitalis Cardenolides and Derivatives.

There is growing interest in exploring Digitalis cardenolides as potential antiviral agents. Hence, we herein investigated the influence of structural features and lipophilicity on the antiherpes activity of 65 natural and semisynthetic cardenolides assayed in vitro against HSV-1. The presence of an α,β-unsaturated lactone ring at C-17, a β-hydroxy group at C-14 and C-3β-OR substituents were considered essential requirements for this biological activity.

Knockout of , Encoding a PRISE (Progesterone 5β-Reductase/Iridoid Synthase-Like Enzyme), Leads to Metabolic Changes in Response to Exogenous Methyl Vinyl Ketone (MVK).

Small or specialized natural products (SNAPs) produced by plants vary greatly in structure and function, leading to selective advantages during evolution. With a limited number of genes available, a high promiscuity of the enzymes involved allows the generation of a broad range of SNAPs in complex metabolic networks. Comparative metabolic studies may help to understand why-or why not-certain SNAPs are produced in plants.